G3BP1 ribonucleoprotein complexes regulate focal adhesion protein mobility and cell migration

Area of Science:

• Cell Biology
• Molecular Biology
• Biochemistry

Background:

• Subcellular mRNA localization is critical for biological processes like cell migration.
• Beta-actin mRNA and ZBP1/IGF2BP1 are known to localize to focal adhesions (FAs) to support cell migration.
• The presence of other mRNAs and RBPs at FAs remains largely unexplored.

Purpose of the Study:

• To identify mRNAs and RNA-binding proteins (RBPs) localized at focal adhesions (FAs).
• To elucidate the mechanism by which these molecules regulate FA function and cell migration.
• To investigate the role of G3BP1-containing ribonucleoprotein complexes (RNPs) in non-stress conditions.

Main Methods:

• Identification of hundreds of mRNAs enriched at FAs (FA-mRNAs) using transcriptomic analysis.
• Characterization of FA-mRNAs' association with stress granule (SG) mRNAs and SG RBPs.
• Investigation of G3BP1's RNA-dependent binding to FA proteins and the role of its domains in RNP formation and FA localization.

Main Results:

• Hundreds of FA-mRNAs were identified, sharing characteristics with stress granule (SG) mRNAs.
• The SG RBP G3BP1 was found to bind FA proteins in an RNA-dependent manner.
• G3BP1's RNA-binding and dimerization domains are crucial for its FA localization and cell migration.
• G3BP1 RNPs enhance cell speed by increasing FA protein mobility and FA size.

Conclusions:

• G3BP1-containing RNPs are recruited to FAs and play a significant role in regulating FA dynamics.
• This recruitment and subsequent regulation of FA proteins by G3BP1 RNPs are essential for efficient cell migration.
• The findings highlight a novel role for G3BP1 RNPs in controlling FA function under normal physiological conditions, beyond their known role in stress granules.